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Biomedical subjects

P Berman

Publications and source records attributed to P Berman.

At least 19 recordsLinked to original sources

A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group.

Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp120 vaccines in 296 HIV-1-uninfected volunteers, including 176 reporting higher HIV-1 risk activities. The immunogens were remarkably well tolerated. After three immunizations, 210 of 241 vaccinees (87%) developed neutralizing antibodies, which persisted in 59% after 2 years. The injection drug users receiving SF-2/gp120 had decreased antibody responses relative to the lower risk groups. Envelope-specific lymphoproliferation peaked after two immunizations, and 54% of vaccinees mounted a DTH reaction to gp120 after 4 years. In summary, these immunogens have low adverse reactogenicity and induce durable antibody and T cell responses to the prototype strains. Unexpected differences in antibody responses among diverse HIV-1 risk strata lend support to the conduct of expanded phase II trials in populations other than low-risk volunteers.

AIDS Vaccines↗

AIDSVAX (MN) in Bangkok injecting drug users: a report on safety and immunogenicity, including macrophage-tropic virus neutralization.

A randomized, double-blind, placebo-controlled phase I/II study of AIDSVAX (MN) was conducted among injecting drug users in Bangkok, Thailand. Four doses of vaccine (300 microg of MN-rgp120 in alum) or placebo (alum) were given at study entry and at 1, 6, and 12 months. The objectives of the study were to evaluate (1) the feasibility of conducting vaccine trials in this population; (2) the safety of this candidate AIDS vaccine; and (3) the immunogenicity of this vaccine. Thirty-three volunteers (22 vaccine and 11 placebo recipients) were recruited. None were lost to follow-up during the 18-month study. Mild reactogenicity was noted, which was similar in both vaccine and placebo recipients. The vaccine induced anti-HIV-1 antibody in all vaccine recipients. Maximal titers of binding antibodies of MN-rgp120 and the V3 domain of MN-rgp120 were induced after the third (6 month) dose while maximal neutralizing antibodies followed the fourth (12 month) dose. The vaccine-induced antibodies from several volunteers were capable of neutralizing macrophage-tropic, subtype B viruses (301660 and JRCSF) detected in a PBMC-based assay. Binding and neutralizing antibodies declined about 10-fold in the 6 months after the last boost. Two vaccinees became infected during the trial, both with subtype E viruses. A phase III efficacy trial, using a bivalent gp120 vaccine containing antigens from a subtype B virus (MN) and a subtype E virus (A244), was initiated in March 1999 in injecting drug users in Bangkok.

AIDS Vaccines↗

Functional recovery of community stroke patients.

PURPOSE: The aims were to describe the functional abilities of and services provided to stroke patients not admitted to hospital a year after stroke and to investigate factors associated with receiving rehabilitation services. METHOD: A cohort of stroke patients who had not been admitted to hospital were notified by general practitioners. Patients were assessed at a month and a year after stroke on measures of impairment and disability. The rehabilitation received was recorded. There were 124 stroke patients notified by GP's who had not been admitted to hospital. Of these 70 were assessed at both one month and one year after stroke. RESULTS: Patients showed persistent impaired levels of disability one year after stroke, as measured by the Extended Activities of Daily Living (EADL) scale. There was no significant improvement in Barthel scores and only a slight improvement on the EADL from one month to one year after stroke. There were no patients with severe mobility or severe arm impairment. Most patients had some cognitive impairment but there was no significant change between a month and a year. The provision of rehabilitation services increased between a month and a year after stroke. Rehabilitation was provided to those patients with impaired motor function. CONCLUSIONS: Stroke patients not admitted to hospital have significant levels of disability which does not change substantially in the year after stroke. Rehabilitation was provided on the basis of physical function, rather than cognitive function.

Chi-Square Distribution↗

Health reform for children: the Egyptian experience with school health insurance.

In June 1992, the People's Assembly of Egypt passed Law 99 expanding health insurance to cover all school children. This was one of the most important initiatives undertaken in recent years by the Ministry of Health, and it effectively increased the number of beneficiaries covered by the Health Insurance Organization (HIO) from 3.75 million in 1988 to about 14 million in 1993. This paper first examines the policy processes for the introduction of this innovation in Egypt's health system. Next, the paper discusses the implementation and consequences of the new policy in terms of coverage, financing, benefits, and delivery of services, along with data on utilization and expenditures. Several important lessons derive from this analysis. First, major reform efforts are possible when there is a strong political commitment and the proposed program and solutions are acceptable to the key stakeholders. Second, compromises and trade-offs are essential to construct a politically feasible and ethically acceptable reform initiative. Third, while these trade-offs might yield short-term gains, the trade-offs in the long term may undermine the reform's capacity to achieve the anticipated equity enhancements and can potentially undermine the financial sustainability of the reform.

Adolescent↗

Comparison of time-efficient CT colonography with two- and three-dimensional colonic evaluation for detecting colorectal polyps.

OBJECTIVE: We compared the findings of time-efficient CT colonography with complete two-dimensional (2D) and three-dimensional (3D) CT colonography and conventional colonoscopy in detecting colorectal polyps. SUBJECTS AND METHODS: Forty-two patients undergoing colonoscopy screening were examined with CT colonography before endoscopy. Data were examined following one of two methods. In method 1, axial 2D data sets were examined in a cine mode. If findings were suggestive of abnormality, focal areas were examined with 3D CT colonography. In method 2, data sets were examined exactly as in method 1, and subsequent to that review, data sets were examined with simultaneous 3D "fly-through" CT colonography (surface-rendered images) and multiplanar reformatted images. The time required to examine CT colonography using each technique was recorded and abnormal findings were documented. Results of methods 1 and 2 were compared with findings on colonoscopy. RESULTS: Colonoscopy detected 16 polyps in 13 patients (polyp size, 2-10 mm). Ten polyps measured 5 mm or less, five measured between 6 and 9 mm, and one measured 10 mm or more. Using method 1, two of 10 polyps measuring less than 5 mm, three of five polyps measuring between 6 and 9 mm, and one polyp measuring 10 mm were detected. We noted no false-positive polyps. Average evaluation time was 16 min. With method 2, the same polyps were seen as with method 1. No additional polyps were detected, and the average evaluation time was 40 min. CONCLUSION: Axial 2D CT colonography can be performed quickly and is comparable with complete 2D and 3D CT colonography in detecting colorectal polyps.

Aged↗

Organization of ambulatory care provision: a critical determinant of health system performance in developing countries.

Success in the provision of ambulatory personal health services, i.e. providing individuals with treatment for acute illness and preventive health care on an ambulatory basis, is the most significant contributor to the health care system's performance in most developing countries. Ambulatory personal health care has the potential to contribute the largest immediate gains in health status in populations, especially for the poor. At present, such health care accounts for the largest share of the total health expenditure in most lower income countries. It frequently comprises the largest share of the financial burden on households associated with health care consumption, which is typically regressively distributed. The "organization" of ambulatory personal health services is a critical determinant of the health system's performance which, at present, is poorly understood and insufficiently considered in policies and programmes for reforming health care systems. This article begins with a brief analysis of the importance of ambulatory care in the overall health system performance and this is followed by a summary of the inadequate global data on ambulatory care organization. It then defines the concept of "macro organization of health care" at a system level. Outlined also is a framework for analysing the organization of health care services and the major pathways through which the organization of ambulatory personal health care services can affect system performance. Examples of recent policy interventions to influence primary care organization--both government and nongovernmental providers and market structure--are reviewed. It is argued that the characteristics of health care markets in developing countries and of most primary care goods result in relatively diverse and competitive environments for ambulatory care services, compared with other types of health care. Therefore, governments will be required to use a variety of approaches beyond direct public provision of services to improve performance. To do this wisely, much better information on ambulatory care organization is needed, as well as more experience with diverse approaches to improve performance.

Adult↗

Engineering Chinese hamster ovary cells to maximize sialic acid content of recombinant glycoproteins.

We have engineered two Chinese hamster ovary cell lines secreting different recombinant glycoproteins to express high levels of human beta1,4-galactosyltransferase (GT, E.C. 2.4.1.38) and/or alpha2, 3-sialyltransferase (ST, E.C. 2.4.99.6). N-linked oligosaccharide structures synthesized by cells overexpressing the glycosyltransferases showed greater homogeneity compared with control cell lines. When GT was overexpressed, oligosaccharides terminating with GlcNAc were significantly reduced compared with controls, whereas overexpression of ST resulted in sialylation of >/=90% of available branches. As expected, GT overexpression resulted in reduction of oligosaccharides terminating with GlcNAc, whereas overexpression of ST resulted in sialylation of >/=90% of available branches. The more highly sialylated glycoproteins had a significantly longer mean residence time in a rabbit model of pharmacokinetics. These experiments demonstrate the feasibility of genetically engineering cell lines to produce therapeutics with desired glycosylation patterns.

Animals↗

Post-processing long pairwise alignments.

MOTIVATION: The local alignment problem for two sequences requires determining similar regions, one from each sequence, and aligning those regions. For alignments computed by dynamic programming, current approaches for selecting similar regions may have potential flaws. For instance, the criterion of Smith and Waterman can lead to inclusion of an arbitrarily poor internal segment. Other approaches can generate an alignment scoring less than some of its internal segments. RESULTS: We develop an algorithm that decomposes a long alignment into sub-alignments that avoid these potential imperfections. Our algorithm runs in time proportional to the original alignment's length. Practical applications to alignments of genomic DNA sequences are described.

Algorithms↗

Financing health services in Poland: new evidence on private expenditures.

This paper estimates total expenditure on health care in Poland in 1994 and provides new evidence on high levels of private spending on health care. The analysis shows that health care expenditures in Poland are higher than has usually been maintained, and are comparable with the prevailing levels in many other European countries. Private expenditure on health is a significant proportion of total expenditure on health, and in particular on financing outpatient care. Available evidence indicates that informal payments made by patients to physicians contribute as much as double of the physician's salary, and thus form an important source of earnings for physicians. This situation of high private expenditures on health care and informal payments to physicians is likely to be true of other transitional economies of Central and Eastern Europe as well. One policy implication that emerges is these transitional economies face a big challenge in managing existing resources, as opposed to finding new resources, in the health sector more effectively to meet the health care needs of their population. The paper highlights the need for better understanding of the current availability and distribution of resources in the health sector and their directions of flow, in both public and private sectors, and suggests using tools such as National Health Accounts to track and monitor changes in the financing of the health care system.

Adolescent↗

Development of a single-shot subunit vaccine for HIV-1. 5. programmable in vivo autoboost and long lasting neutralizing response.

The subunit vaccine for HIV-1, recombinant glycoprotein 120 (rgp120), was used as a model antigen to evaluate the potential for a pulsatile single immunization vaccine formulation consisting of poly(lactic-co-glycolic) acid (PLGA) microspheres. We designed rgp120 PLGA microsphere formulations that provide a pulse of rgp120 at 1 to 6 months (depending on the polymer) after administration, mimicking another immunization. In these studies, the in vitro pulse of rgp120 correlated well with the observed in vivo autoboost as measured by an increase in anti-gp120 antibodies in guinea pigs. The immune response to the rgp120 PLGA microsphere formulations was increased by adding the soluble form of the saponin-derived adjuvant, QS-21. The use of small microspheres, however, did not increase the humoral response to rgp120. A single immunization with rgp120 PLGA microspheres resuspended in soluble rgp120 and QS-21 elicited neutralizing antibody titers that were comparable to titers obtained from two immunizations of rgp120 and QS-21 at the same total dose. Administration of rgp120 PLGA microspheres in baboons resulted in high, long-lasting neutralizing antibody titers that were greater than repeated immunizations with soluble rgp120 and QS-21. These studies also indicated that a continuous release of QS-21 at the injection site may provide a greater immune response than a bolus injection. Overall, this work demonstrated that PLGA microsphere formulations may be designed to provide in vivo pulses of an antigen eliminating the need for repeated immunizations.

AIDS Vaccines↗

Alignments without low-scoring regions.

Given a strong match between regions of two sequences, how far can the match be meaningfully extended if gaps are allowed in the resulting alignment? The aim is to avoid searching beyond the point that a useful extension of the alignment is likely to be found. Without loss of generality, we can restrict attention to the suffixes of the sequences that follow the strong match, which leads to the following formal problem. Given two sequences and a fixed X > 0, align initial portions of the sequences subject to the constraint that no section of the alignment scores below -X. Our results indicate that computing an optimal alignment under this constraint is very expensive. However, less rigorous conditions on the alignment can be guaranteed by quite efficient algorithms. One of these variants has been implemented in a new release of the Blast suite of database search programs.

Algorithms↗

Private health care provision in developing countries: a preliminary analysis of levels and composition.

While the importance of the private sector in providing health services in developing countries is now widely acknowledged, the paucity of data on numbers and types of providers has prevented systematic cross-country comparisons. Using available published and unpublished sources, we have assembled data on the number of public and private health care providers for approximately 40 countries. This paper presents some results of the analysis of this database, looking particularly at the determinants of the size and structure of the private health sector. We consider two different types of dependent variable: the absolute number of private providers (measured here as physicians and hospital beds), and the public-private composition of provision. We examine the relationship between these variables and income and other socioeconomic characteristics, at the national level. We find that while income level is related to the absolute size of the private sector, the public-private mix does not seem to be related to income. After controlling for income, certain socioeconomic characteristics, such as education, population density, and health status are associated with the size of the private sector, though no causal relationship is posited. Further analysis will require more complete data about the size of the private sector, including the extent of dual practice by government-employed physicians. A richer story of the determinants of private sector growth would incorporate more information about the institutional structure of health systems, including provider payment mechanisms, the level and quality of public services, the regulatory structure, and labour and capital market characteristics. Finally, a normative analysis of the size and growth of the private sector will require a better understanding of its impact on key social welfare outcomes.

Delivery of Health Care↗

Rehabilitation needs of community stroke patients.

PURPOSE: The aim was to identify stroke patients not admitted to hospital, to assess their disabilities and the rehabilitation provided. METHOD: Stroke patients were notified by General Practitioners, assessed a month after stroke on measures of impairment and disability and the rehabilitation received was recorded. There were 124 patients notified and 93 assessed. RESULTS: Patients showed an average decline of 1.7 on the Barthel Index and 3.6 on the Extended Activities of Daily Living scale from before to after stroke. There were 27% with severe mobility problems and 47% with clinically relevant arm impairment. Many patients had cognitive impairment with only 9% having no deficit. Mood problems were less common with 26% anxious and 13% depressed. Significant stress occurred in 15% of carers. The provision of rehabilitation was low and there was poor correspondence between impairments and services provided. CONCLUSION: There is an unmet potential for rehabilitation in stroke patients not admitted to hospital.

Activities of Daily Living↗